Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways

Abstract

Natural chalcones possess antitumor properties and play a role as inducers of apoptosis, antioxidants and cytotoxic compounds. We recently reported that novel nitrogen chalcone-based compounds, which were generated in our lab, have specific effects on triple-negative breast cancer cells. However, the outcome of these two new compounds on human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains nascent. Thus, we herein investigated the effects of these compounds (DK-13 and DK-14) on two HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data revealed that these compounds inhibit cell proliferation, deregulate cell-cycle progression and significantly induce cell apoptosis in both cell lines. Furthermore, the two chalcone compounds cause a significant reduction in the cell invasion ability of SKBR3 and ZR75 cancer cells. In parallel, we found that DK-13 and DK-14 inhibit colony formation of both cell lines in comparison to their matched controls. On the other hand, we noticed that these two compounds can inhibit angiogenesis in the chorioallantoic membrane model. The molecular pathway analysis of chalcone compounds exposed cells revealed that these compounds inhibit the expression of both JNK1/2/3 and ERK1/2, the major plausible molecular pathways behind these events. Our findings implicate that DK-13 and DK-14 possess effective chemotherapeutic outcomes against HER2-positive breast cancer via the ERK1/2 and JNK1/2/3 signaling pathways.

2-bromo-2’5’-dihydroxychalcone analogue Inhibits Endothelial Migration by Targeting VEGF-induced ERK 1/2 Phosphorylation

“…Chemical scaffolds such as chalcones have shown to exhibit antiangiogenic activity via downregulation of VEGFR-2 and signalling mediators such as ERK ½ (Mojzis et al, 2008; Lee et al, 2012; Mahapatra, Bharti and Asati, 2015). Recent studies have shed light on new chalcones derivatives that have been shown to inhibit the expression of ERK ½. Rizeq and colleagues reported novel nitrogen based chalcones capable of inhibiting angiogenesis in chorioallantoic membrane model (CAM) via targeting JNK 1/2/3 and ERK ½ (Rizeq et al, 2021). Kuruc and colleagues identified antimigratory activity of a novel phenolic chalcone L1 against Human cervical carcinoma cells (HeLa) and attributed the modulation of Akt, JNK, p38 and ERK ½ to the activity observed (Kuruc et al, 2021).…”